Isoxazolo pyrazines

Isoxazolo[4,5-6]pyrazine (176) is resistant to electrophilic halogenation because the potentially reactive site is at the ring junction. The 7-oxide, though, was converted into the 6-chloro derivative of 176 on heating with phosphoryl chloride (73JHC181). 

Isoxazolo[5,4-, [l,2,4]triazine-4-ones are prepared by six-membered cyclizations of diazonium salts onto adjacent ester or amide substituents on the isoxazole ring (Section 10.13.9.1.2(i)). [l,2,5]Oxadiazolo[3,4- ]pyrazines (Section 10.13.9.1.2(ii)) and [l,2,5]oxadiazolo[3,4- pyridazines (Section 10.13.9.1.2(iii)) are traditionally accessed by reliable six-membered condensation reactions to give the fused pyrazine and pyridazine rings, respectively. 

Thiazolo[5,4-d]pyrimidine l//-Pyrazolo[3,4-b]pyrazine Isoxazolo[4,5-fc]pyrazine... 

Isoxazolo[3,4-b]pyrazine Isothiazolo[4,5-b ]pyrazine Isothiazolo[3,4-f>]pyrazine... 

The only examples of this synthesis employed isoxazolopyrazine substrates that were themselves made from pyrazines. Thus l-benzyl-5,6-dihydro-2(l//)-pyrazi-none 4-oxide (99) underwent addition by ethynylbenzene to give 5-benzyl-2-phemi-6,7-dihydro-3a//-isoxazolo[2,3-a]pyrazin-4(5//)-onc (100) (60%), which subsequently underwent ring cleavage by molybdenum hexacarbonyl in wet acetonitrile to afford l-benzyl-3-phenacyl-3,4,5,6-tetrahydro-2(l//)-pyrazinone (101) in 54% yield several analogues were made similarly.1539... 

Like the foregoing isomeric substrates (Section 2.2.7), these isoxazolopyrazines were frequently made from pyrazines. Thus 3-(/V-hydroxyamidino)-2(l//)-pyrazi-none (102) was converted in two stages into isoxazolo[4,5-b]pyrazin-3-aminc (103), which on vigorous treatment with acetic anhydride afforded 2-acetoxy-3-(5-methyl-l,2,4-oxadiazol-3-yl)pyrazine (104) in 78% yield the same substrate (103) in hot formic acid for 5 min gave mainly 3-(l,2,4-oxadiazol-3-yl)-2(l/7)-pyrazi-none (105) (50%) but if heating was prolonged for 3 h only 3-oxo-3,4-dihydro-2-pyrazinecarbonitrile (106) was obtained, presumably via the oxadiazolopyrazine (105).1115... 

Diethyl-5-methyl-3,6-dihydro-2(l//)-pyrazinone 4-oxide (301) gave dimethyl 4,4-diethyl-3a-methyl-6-oxo-4,5,6,7-tetrahydro-3a/7-isoxazolo[2,3-a]pyrazine-2,3-dicarboxylate (302) (Me02CC CC02Me, CHC13, reflux, 3 h 64%) 544 homologues likewise.544... 

Isoxazolo[4,5-ft]pyrazine is prepared from 3-methylisoxazole-4,5-diamine with glyoxal and sodium hydrogen sulfite in 50% yield. ... 

Amine 32 was obtained on interaction of compound 14 (R = Ph) with hydrazine closure of the pyrazine ring and withdrawing of the phthaloyl protection are simultaneous processes. Photolysis or thermolysis of 1-arylazo-8-azidonaphthalenes gives rise to benzole, J]indazole N-arylim-ines (78JOC2508 [Eq. (8)]. As a result of a complicated photochemical rearrangement, isoxazolo[5,4-fe]pyridine derivative (33) is converted to N-aminopyrazole 34 in 60% yield (88H1899). 

Isoxazolo[5,4-c]pyridine 6, 617-634, 633 7 1 C3NS-C4N2 Isothiazolo[4,5-6]pyrazine 6,640... 

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